Peripheral and ocular microvascular alterations in systemic sclerosis: observations from capillaroscopic assessments, perfusion peripheral analysis, and optical coherence tomography angiography.

To investigate the correlations between finger microvascular morphology and function in patients with systemic sclerosis (SSc) and the status of ocular microcirculation, as detected by nailfold videocapillaroscopy (NVC), laser speckle contrast analysis (LASCA), and optical coherence tomography angiography (OCTA). The enrollment included 32 SSc patients, classified according to the 2013 ACR/EULAR criteria, and 27 sex- and age-matched healthy controls. The participants underwent comprehensive rheumatological and ophthalmological examinations, as well as NVC, LASCA, and OCTA analysis on the same day at a single center from March to October 2022. SSc patients receiving intravenous prostanoids cycles were assessed at least 1 month after infusion. Statistical analysis was conducted using Stata® 15.1. Significant direct correlations were observed between the mean capillary number (at NVC) and the mean perfusion of fingers (at LASCA) with the retinal and choroidal perfusion (at OCTA) (all p < 0.05). In addition, a significantly reduced retinal and choroidal perfusion was detected in SSc patients vs controls (all p < 0.05). Interestingly, diffuse cutaneous SSc (dcSSc) patients exhibited a lower choroidal perfusion (p = 0.03) but an increased choroidal thickness (CT) than limited cutaneous SSc patients (p < 0.001). CT was increased also in patients with positive Scl70 antibodies and with a history of digital ulcers directly correlating with disease duration (r = 0.67, p = 0.001). Finally, the combination of LASCA and OCTA parameters showed a significant discrimination capacity between SSc patients and controls, with an area under the curve of 0.80 [95% CI (0.74, 0.87)]. Peripheral microvascular damage is correlated with impaired ocular microcirculation in SSc. The increased choroidal thickness observed in dcSSc may be related to local sub-endothelial extracellular matrix deposition. The combined analysis of choroidal and fingertip perfusion offers preliminary insights that may complement traditional diagnostic methods for SSc.

Evaluation of peripapillary vascular flow in patients with Thyroid-Associated Ophthalmopathy (TAO) by OCT Angiography.

PURPOSE: To evaluate changes in peripapillary vascular blood flow indices (PVBFI) in patients with thyroid-associated ophthalmopathy (TAO) using OCT angiography (OCTA) technology. METHODS: Patients with TAO and control subjects matched for age and sex were included in the study. Eye examination, Clinical Activity Score (CAS) evaluation and OCTA scan analysis (Topcon ImageNet 6; DRI OCT Triton, Topcon Corporation) were performed. In particular, PVBFI of the superficial capillary plexus (SCP), deep capillary plexus (DCP), outer retina (OR) and choriocapillaris (CC) layers were obtained by OCTA and extracted from 8-bit greyscale OCT images using the ImageJ software package. RESULTS: Twenty-six patients with TAO (19 females, mean age 54.7 ± 5.2 and 7 males, mean age 51.4 ± 16.3) were compared with 26 healthy subjects (15 females, mean age 48.2 ± 14.1 and 11 males, mean age 53.1 ± 15.2). Both DCP-PVBF and CC-PVBFI were significantly reduced in TAO patients compared to control eyes (28.6 ± 2.1 vs. 29.7 ± 0.93, p = 0.002; 46.5 ± 1.72 vs. 47.2 ± 1.2, p = 0.019 respectively); on the other hand, no statistically significant differences were found in SCP-PVBFI and OR-PVBFI in TAO patients compared to healthy subjects (p > 0.05). Also, CC-PVBFI was associated with elevated values of CAS (p = 0.018) and ROC curve showed that patients with elevated CC-PVBFI were correlated with active TAO (CAS > 3) (p = 0.012). CONCLUSIONS: TAO disease may be associated with changes in DCP-PVBFI and CC-PVBFI; also, CC-PVBFI seems to correlate with disease activity.

Macular Choroidal Thickness: Evaluation of Variability among Measurements and Assessment of Predictive Value of Glaucomatous Visual Field Damage.

INTRODUCTION: This study aimed to investigate the relationship between the choroidal circulation and glaucoma, assessing macular choroidal thickness (MCT) as a predictive value of glaucomatous visual field damage. METHODS: Twenty primary open-angle glaucoma patients were recruited. Patients underwent 2 SS-OCT scans: one with DRI OCT (Topcon) and the other with PLEX Elite 9000 (Zeiss). Standard OCT parameters were acquired by DRI OCT, while MCT was manually measured in 5 points on Plex ELITE 9000 images. The relationship among MCT, standard OCT parameters, and visual field indices was evaluated. Pearson's r correlation was calculated to evaluate these relationships. Reproducibility of measurements was analyzed. RESULTS: MCT measurements showed a good intra- and interobserver repeatability. A negative correlation appeared between MCT and BMI (r = -0.518, p = 0.023). Mean deviation showed a statistically significant correlation with MCT measured at subfoveal and at 1,000 µm nasally (r = 0.50, p = 0.03, and r = 0.52, p = 0.023). A correlation was found between the 2 MCT (Zeiss vs. Topcon) measurements and between MCT and peripapillary choroidal thickness (r = 0.944 and r = 0.740, p < 0.001, respectively). CONCLUSIONS: A good intra- and interobserver reproducibility was found. MCT showed a weak predictive value of glaucomatous visual field damage. A significant correlation was found between MCT and BMI.

Concerns on ranibizumab and zoledronic acid safety for experimentally treating women with endometriosis.

Correspondence to the original research entitled "Effects of ranibizumab and zoledronic acid on endometriosis in a rat model" published by Ozdemir et al.

The diterpene Manool extracted from Salvia tingitana lowers free radical production in retinal rod outer segments by inhibiting the extramitochondrial F1 Fo ATP synthase.

Uncontrolled oxidative stress production, especially in the outer retina is one of the causes of retinal degenerations. Mitochondria are considered the principal source of oxidative stress. However, a Reactive Oxygen Intermediates (ROI) production in the retinal photoreceptor layer seems to depend also on the expression of an extramitochondrial oxidative phosphorylation (OxPhos) machinery in the rod outer segments (OS). In fact, OS conduct aerobic metabolism, producing ATP through oxygen consumption, although it is devoid of mitochondria. As diterpenes display an antioxidant effect, we have evaluated the effect Manool, extracted from Salvia tingitana, on the extramitochondrial OxPhos and the ROI production in the retinal rod OS. Results confirm that the OxPhos machinery is ectopically expressed in the OS and that F1 Fo -ATP synthase is a target of Manool, which inhibited the OS ATP synthesis, binding the F1 moiety with high affinity, as analysed by molecular docking. Moreover, the overall slowdown of OxPhos metabolism reduced the ROI production elicited in the OS by light exposure, in vitro. In conclusion, data are consistent with the antioxidant properties of Salvia spp., suggesting its ability to lower oxidative stress production, a primary risk factor for degenerative retinal diseases. SIGNIFICANCE OF THE STUDY: Here we show that Manool, a diterpene extracted from Salvia tingitana has the potential to lower the free radical production by light-exposed rod outer segments in vitro, by specifically targeting the rod OS F1 Fo -ATP synthase belonging to the extramitochondrial OxPhos expressed on the disk membrane. The chosen experimental model allowed to show that the rod OS is a primary producer of oxidative stress linked to the pathogenesis of degenerative retinal diseases. Data are also consistent with the antioxidant and anti-inflammatory action of Salvia spp., suggesting a beneficial effect also in vivo.

Vascular Density and Retinal Function in Patients with Retinitis Pigmentosa Evaluated by Swept-Source OCT Angiography and Microperimetry.

PURPOSE: To determine the retinal and choroidal vessel density in the macular area with swept-source optical coherence tomography (OCT) angiography (SS-OCTA) in patients affected by retinitis pigmentosa (RP), to compare their data with those on healthy subjects, and to study a possible morphofunctional correlation by microperimetry (MP-1). METHODS: A total of 40 eyes of 40 patients affected by RP and 24 eyes of 24 healthy subjects were included in the study. Manually moving down the segmentation line of the SS-OCTA, we have evaluated the vessel density for the superficial retinal plexus, deep retinal plexus, choriocapillaris, and three levels of the choroid. RESULTS: Linear regression analyses were performed of the retinal structure and function. No significant correlation was detected in any case (R2 = 0, p > 0.05). A comparison between RP and healthy controls revealed a significant reduction in SS-OCTA mean capillary density in the RP group (p = 0.0011). This relationship was consistent across vascular layers (p = 0.2413). A significant association between the capillary density of the various vascular complexes was detected within individual eyes (p < 0.0001). CONCLUSIONS: This study represents the first comparing MP-1 and SS-OCTA data in the largest cohort of patients. RP patients showed a reduction in both the retinal and the choroidal vascular network in the macular area compared to healthy subjects.

Hydroxychloroquine and chloroquine retinal safety concerns during COVID-19 outbreak.

PURPOSE: The current coronavirus disease 2019 (COVID-19) has been declared by the World Health Organization a global pandemic. Chloroquine (CQ) and hydroxychloroquine (HCQ) have been largely adopted in the clinical setting for the management of SARS-CoV-2 infection; however, their known retinal toxicity has raised some safety concerns, especially considering the higher-dosage employed for COVID-19 patients as compared with their suggested posology for their usual indications, including systemic lupus erythematosus and other rheumatic diseases. In this review, we will discuss the optimal dosages recommended for COVID-19 patients when treated with HCQ and CQ. METHODS: A comprehensive literature search was performed in PubMed, Cochrane library, Embase and Scopus, by using the following search terms: "chloroquine retinal toxicity" and "hydroxychloroquine retinal toxicity" alone or in combination with "coronavirus", "COVID-19", " SARS-CoV-2 infection " from inception to August 2020. RESULTS: Although there is still no consistent evidence about HCQ/CQ retinal toxicity in patients with COVID-19, these possible drug-related retinal adverse events may represent a major safety concern. For this reason, appropriate screening strategies, including telemedicine, should be developed in the near future. CONCLUSION: A possible future clinical perspective for patients with COVID-19 treated with HCQ/CQ could reside in the multidisciplinary collaboration between ophthalmologists monitoring the risk of HCQ/CQ-related retinal toxicity and those physicians treating COVID-19 infection.

Evaluation of choroidal thickness and choroidal vascular blood flow in patients with thyroid-associated orbitopathy (TAO) using SD-OCT and Angio-OCT.

PURPOSE: The aim of this study was to evaluate changes in choroidal thickness and in choroidal vascular blood flow in patients with thyroid-associated orbitopathy (TAO) and their relationship with clinical features and disease activity using spectral domain optical coherence tomography (SD-OCT) and Angio-OCT technology. METHODS: Eighteen patients and control subjects underwent a complete eye examination, OCT, and Angio-OCT. We also obtained angiographic scans at 3 different consecutive levels (L1, L2, and L3) below the choriocapillary. RESULTS: The subfoveal choroid was significantly thicker in TAO patients than the control eyes (285.6275 ± 32.5 µm compared with 135.89 ± 19.8 µm, respectively, p = 0.0089). The correlation analysis in the TAO group showed a significant correlation between the choroidal thickness and EUGOGO clinical score (r = 0.84, p = 8.44032E-07). Vascular flow of choriocapillary was markedly reduced in subjects with TAO compared with healthy subjects (49.78 ± 4.5 vs. 53.36 ± 1.07; p = 2.5105E-07) and vascular flow of the deeper layer L3 resulted higher in subjects with TAO than in healthy subjects (46.9 ± 20.23 and 41.475 ± 3.06; p = 0.01168). CONCLUSIONS: Subfoveal choroidal thickness and choroidal blood flow were significantly different in patients with TAO compared with healthy subjects.

Real-Life Data in the Treatment of Neovascular Age-Related Macular Degeneration: Results from the Imaculaweb Registry Evaluated in a Single Italian Medical Retina Center.

INTRODUCTION: The aim of this study is to assess and compare the long-term clinical efficacy of anti-VEGF drugs using the Imaculaweb registry. METHODS: In this observational study based on the Imaculaweb registry, outcome measures were the number of injections, the change in mean visual acuity (VA) and central macular thickness (CMT), and the time between diagnosis and the first injection. RESULTS: In total, 126 eyes of 109 patients were included in the study. The mean VA was 49.4 ± 21.4, 54.1 ± 22.2, 51.6 ± 24.9, and 48.3 ± 25.7 letters at baseline and at the 1-, 2-, and 3-year follow-ups, respectively. Significant VA increases (p = 0.0002 for the first year and p = 0.045 for the second year) were documented at years 1 and 2 but not at year 3 (p = 0.8). The mean number of injections was 5.2, 2.6, and 2.3 at the 1-, 2-, and 3-year follow-ups, respectively. In the first year, 30% of the patients received at least 7 injections, while only 6.4% received <3 injections. CMT decreased significantly during the overall follow-up period, and intra- and subretinal fluid decreased (p < 0.0001). CONCLUSION: Imaculaweb turned out to be an effective tool to collect and share clinical data as well as to monitor patient outcome.

An update on pharmacological treatment options for amblyopia.

Amblyopia is a common cause of visual impairment in children and young adults. The cornerstone in the management of this disorder is based on increasing visual stimulation of the amblyopic eye by occlusion, by administering atropine or by causing optical penalization of the dominant eye. All these treatment options have shown some limits in terms of efficacy, due to the suboptimal treatment adherence for the patients and the lack of long-term clinical outcomes. Moreover, although it is well known that clinical efficacy decreases with age, new evidence is suggesting that cortical plasticity can be induced also in older children. For these reasons, new treatment options are being studied, in order to extend the "treatment window" beyond the critical period also in older patients. In this review, we will discuss all the most promising novel pharmacological agents in the management of amblyopia.

Bleb Needling with Mitomycin C as Adjunctive Therapy in Failing Blebs: A Retrospective Study.

PURPOSE: To evaluate the effects and complications related to use of mitomycin C (MMC) as an adjunctive therapy in bleb needling. METHODS: Retrospective review of the records of patients affected by open-angle glaucoma who underwent a bleb revision as a treatment for failed trabeculectomy. All subjects underwent surgery with a fornix-based approach to incision. Full baseline data for each patient included a comprehensive ocular and medical history, the patient's Snellen visual acuity test results, and Goldmann applanation tonometry test results. Data were reported following observations occurring at 6, 12, 18, 24, and 30 months. In addition, the number and timing of needling with or without MMC subconjunctival injections and any short- and long-term complications were observed. RESULTS: We included 101 patients, 56 (55.4%) male and 45 (44.6%) female. The mean age was 69.81 ± 16.19 years (range 28-92). Statistically significant effects of needling and needling and MMC (p values <0.05) in the decrease in intraocular pressure were observed. Three (2.9%) patients presented hypotony at the last follow-up visit. No other complications were observed. CONCLUSIONS: Needling bleb revision augmented with the use of MMC appears to be a more useful tool in the management of failing bleb.

Chorioretinal folds: a proposed diagnostic algorithm.

PURPOSE: To create a diagnostic algorithm for the management of chorioretinal folds. METHODS: We reviewed the existing literature about chorioretinal folds focusing our attention on three specific conditions and created a diagnostic algorithm in order to otpimize the choice and the number of investigations. RESULTS: Chorioretinal folds are visible striations of the fundus usually arranged in parallel lines and disposed horizontally. They may be either unilateral or bilateral, symptomatic or asymptomatic and are often associated with different possible ocular and extra ocular pathologies, including systemic diseases like autoimmune disorders and intracranial hypertension. They are named idiopathic when no apparent cause for their development is detectable. However, with improved diagnostic testing, the patients with idiopathic choroidal folds are likely to represent only a smaller portion of the total. CONCLUSIONS: Since choroidal folds be the sole sign of an underlying disease possibly requiring a multidisciplinary approach, an appropriate work-up varying according to the specific clinical features of each case is needed to define the etiology and the treatment. A diagnosting algorithm may be useful in order to optimize the diagnostic approach and management.

Prospective evaluation of CO2 laser-assisted sclerectomy surgery (CLASS) with Mitomycin C.

PURPOSE: Our purpose was to evaluate the clinical safety and efficacy of CO2 laser-assisted sclerectomy surgery (CLASS) with Mitomycin C (MMC) in open angle glaucoma (OAG). METHODS: This was a prospective, uncontrolled, interventional case series. All subjects underwent CLASS procedure by a single surgeon. After the dissection of a partial thickness scleral flap, topical MMC 0.2 mg/ml was applied to the sclera and the conjunctiva for 3 min. The CO2 laser with a beam-manipulating system was used to ablate the scleral tissue and expose the Schlemm's canal area. Primary outcomes: intraocular pressure (IOP) change, number of IOP-lowering medicaments change. Adverse events were evaluated as secondary outcomes. RESULTS: Twenty-one eyes of 21 patients underwent the CLASS procedure. Thirteen were primary OAG (62%), two normal pressure glaucoma (10%), three exfoliative glaucoma (14%) and three others secondary OAG. With a mean (SD) follow-up of 15.3 (5.9) months, the IOP changed from 25.4 (6.7) mmHg at baseline to 10.9 (3.4) mmHg al the last visit. Mean reduction of IOP was -14.5 mmHg (95% CI, -17.7 to -11.2, P < 0.001). The median (IQR) number of IOP-lowering medication decreased from 3 (3-3) at baseline to 1 (0-1) at the last visit (P < 0.001). Visual acuity did not change significantly. Adverse events: five eyes (24%) developed iris adhesion to the filtration area that was successfully managed with office-based procedures. In one case (5%), CLASS was converted to trabeculectomy due to intraoperative perforation of the ablated area. There was one case of hypotony maculopathy successfully treated with placement of additional transconjunctival scleral flap sutures. CONCLUSIONS: The CLASS procedure with MMC is clinically safe and effective maintaining a large reduction in IOP and in the number of IOP-lowering medications with a mean follow-up of 15 months. Iris adhesion at the filtrating area warrants further evaluation and possibly reflects the surgeon's learning curve.

The Outflow Pathway: A Tissue With Morphological and Functional Unity.

The trabecular meshwork (TM) plays an important role in high-tension glaucomas. Indeed, the TM is a true organ, through which the aqueous humor flows from the anterior chamber to Schlemm's canal (SC). Until recently, the TM, which is constituted by endothelial-like cells, was described as a kind of passive filter. In reality, it is much more. The cells delineating the structures of the collagen framework of the TM are endowed with a cytoskeleton, and are thus able to change their shape. These cells also have the ability to secrete the extracellular matrix, which expresses proteins and cytokines, and are capable of phagocytosis and autophagy. The cytoskeleton is attached to the nuclear membrane and can, in millionths of a second, send signals to the nucleus in order to alter the expression of genes in an attempt to adapt to biomechanical insult. Oxidative stress, as happens in aging, has a deleterious effect on the TM, leading eventually to cell decay, tissue malfunction, subclinical inflammation, changes in the extracellular matrix and cytoskeleton, altered motility, reduced outflow facility, and (ultimately) increased IOP. TM failure is the most relevant factor in the cascade of events triggering apoptosis in the inner retinal layers, including ganglion cells. J. Cell. Physiol. 231: 1876-1893, 2016. © 2016 Wiley Periodicals, Inc.

Response to anti-VEGF-A treatment of endothelial cells in vitro.

This study was conducted to compare the effects of two anti-VEGF-A drugs, Ranibizumab and Aflibercept, on the expression and secretion of VEGFs family members, and on their influence in proliferation and migration of endothelial cells (HECV) in vitro. HECV cells were exposed 24 h (T1), 4 days (T2) and 6 days (T3) to Ranibizumab or Aflibercept at pharmacodynamically relevant concentrations (Ranibizumab: 12.5 µg/ml and 125 µg/ml; Aflibercept: 50 µg/ml and 500 µg/ml). Cell viability and then expression and secretion of VEGF-A, VEGF-B, VEGF-C and PlGF were evaluated respectively by Real Time-PCR and ELISA. Intracellular signaling activated by VEGF-A and VEGF-C was investigated evaluating phosphorylation of VEGFR2. Influence in would healing was evaluated through scratch assay. In general no differences were observed among the tested concentrations of anti-vegf drugs. Ranibizumab and Aflibercept did not affect HECV cell viability in all experimental times. At T1, Ranibizumab decreased mRNA levels of VEGF-A, induced VEGF-C secretion, abrogated phosphorylation of VEGFR2 stimulated by VEGF-A, and impaired ability of HECV cells to repair wound healing. Aflibercept decreased mRNA levels of VEGF-A, -B and PlGF; slightly increased basal level of phVEGFR2, and completely abrogated phosphorylation stimulated by VEGF-A and VEGF-C. No effects on secretion of VEGF-B and on would healing were observed after exposure to Aflibercept. Prolonged exposure to anti-VEGFs decreased expression and secretion of VEGF-A and VEGF-B, up-regulated VEGF-C mRNA levels and its secretion, and increased basal phosphorylation of VEGFR2. Acute treatment with Ranibizumab or Aflibercept evoked different responses on endothelial cells, however these differences were lost after prolonged exposure. Scratch test results suggest that treatment with Ranibizumab may be more effective than Aflibercept in reducing angiogenic potential of endothelial cells in vitro.

Evaluation of oxidative stress levels in the conjunctival epithelium of patients with or without dry eye, and dry eye patients treated with preservative-free hyaluronic acid 0.15 % and vitamin B12 eye drops.

PURPOSE: Increased levels of oxidative stress have been seen in animal models of dry eye and in the conjunctival epithelial cells of patients with Sjögren's syndrome. The aims of this study were to compare the levels of oxidative stress in patients with dry eye and patients without dry eye and to evaluate the effects of treatment with preservative-free eye drops containing hyaluronic acid 0.15 % and vitamin B12 on oxidative stress and dry eye symptoms. METHODS: Three cohorts of patients who were to undergo planned cataract surgery were enrolled: patients with dry eye randomized to either no treatment (n = 29) or treatment (n = 32) with hyaluronic acid/vitamin B12 eye drops, and patients without dry eye (n = 42). Patients were assessed by Schirmer's type I test, fluorescein clearance test (FCT), Break Up Time (BUT), and Ocular Surface Disease Index (OSDI). Lipid peroxidation, a marker of oxidative stress, was assessed by LP-CHOLOX test. RESULTS: Compared with patients without dry eye, patients with dry eye had significantly increased levels of oxidative stress, higher OSDI and FCT scores, and significantly lower Schirmer's test and BUT scores. Treatment with eye drops containing hyaluronic acid 0.15 % and vitamin B12 was associated with significantly reduced levels of oxidative stress and OSDI and FCT scores and significantly increased Schirmer's test and BUT scores. CONCLUSIONS: These findings indicate that oxidative stress is associated with dry eye and that hyaluronic acid/vitamin B12 eye drops may attenuate oxidative stress and inflammation, improving dry eye symptoms. Further study in controlled clinical trials is warranted.

Combining macula clinical signs and patient characteristics for age-related macular degeneration diagnosis: a machine learning approach.

BACKGROUND: To investigate machine learning methods, ranging from simpler interpretable techniques to complex (non-linear) "black-box" approaches, for automated diagnosis of Age-related Macular Degeneration (AMD). METHODS: Data from healthy subjects and patients diagnosed with AMD or other retinal diseases were collected during routine visits via an Electronic Health Record (EHR) system. Patients' attributes included demographics and, for each eye, presence/absence of major AMD-related clinical signs (soft drusen, retinal pigment epitelium, defects/pigment mottling, depigmentation area, subretinal haemorrhage, subretinal fluid, macula thickness, macular scar, subretinal fibrosis). Interpretable techniques known as white box methods including logistic regression and decision trees as well as less interpreitable techniques known as black box methods, such as support vector machines (SVM), random forests and AdaBoost, were used to develop models (trained and validated on unseen data) to diagnose AMD. The gold standard was confirmed diagnosis of AMD by physicians. Sensitivity, specificity and area under the receiver operating characteristic (AUC) were used to assess performance. RESULTS: Study population included 487 patients (912 eyes). In terms of AUC, random forests, logistic regression and adaboost showed a mean performance of (0.92), followed by SVM and decision trees (0.90). All machine learning models identified soft drusen and age as the most discriminating variables in clinicians' decision pathways to diagnose AMD. CONCLUSIONS: Both black-box and white box methods performed well in identifying diagnoses of AMD and their decision pathways. Machine learning models developed through the proposed approach, relying on clinical signs identified by retinal specialists, could be embedded into EHR to provide physicians with real time (interpretable) support.

Prechoroidal Cleft Regression After Switch to Intravitreal Brolucizumab.

INTRODUCTION: Prechoroidal cleft has been described as a negative prognostic biomarker in patients affected with neovascular age related macular degeneration (nAMD). This peculiar finding consists of a lenticular hyporeflective space located between an outward bowing of Bruch's membrane and the base of a fibrovascular retinal pigment epithelium detachment (PED). Previous studies have reported the partial or complete regression of prechoroidal clefts after treatment with anti-vascular endothelial growth factor (VEGF) injections. CASE REPORT: To report a case of complete anatomical regression of an unresponsive prechoroidal cleft after switching to intravitreal Brolucizumab. The patient maintained cleft regression over time and no adverse events (i.e., RPE tears, intraocular inflammation) were observed during follow-up. CONCLUSIONS AND IMPORTANCE: To our knowledge, this case report is the first to analyze the clinical efficacy of brolucizumab targeting prechoroidal clefts. Clinical implication and pathogenesis of prechoroidal clefts are yet to be fully elucidated.

Predictors of 24-month onset of macular fibrosis in type 3 macular neovascularisation.

AIMS: To explore prognostic multimarker models for progression to macular fibrosis (MF) over 24 months specific to type 3 macular neovascularisation (T3 MNV). METHODS: This retrospective, exploratory, single-centre, cohort study comprised 65 eyes of 43 Caucasian patients with treatment naive T3 MNV, all with a 24-month follow-up post anti-VEGF therapy using a strict pro-re-nata (PRN) regimen. Data on demographic features, clinical findings, frequency of intravitreal treatments and optical coherence tomography biomarkers were collected at baseline and after 12 and 24 months of follow-up. Logistic regression models (LRM) and receiver-operating curve (C-index) analyses were performed to evaluate the prognostic ability of the studied biomarkers in discriminating between MF affected and unaffected patients. RESULTS: At final follow-up, MF was present in 46.2% of eyes. Subretinal hyper-reflective material (SHRM) and subretinal pigment epithelium multilaminar hyper-reflectivity (multilaminae) emerged as significant predictors for MF, with adjusted odds ratios (OR) of 18.0 (95% CL 13.4 to 24.1) and 11.8 (95% CL 8.66 to 16.0), respectively. Additionally, the presence of multifocal lesions (OR 0.04, 95% CL 0.01 to 0.30) appeared to decrease the likelihood of MF. C-indexes for the selected LRMs ranged between 0.92 and 0.88, indicating a comparably high discriminant ability. Despite consistent treatment schedules between the two groups (MF: median intravitreal treatment (IVT) number=10.5, IQR=7; non-MF: median IVT=10, IQR=6), a decline in best-corrected visual acuity was noted in the group with MF onset over the 24-month follow-up (-13.0 ETDRS letters; 95% CL -22.1 to -3.9; p=0.006). CONCLUSION: Our study identifies SHRM and multilaminae as relevant predictors of 24-month onset of MF in patients with T3 MNV. These findings enrich our understanding of the development of MF in T3 MNV and can guide improved risk prognostication. Future research should consider larger samples and prospective designs to validate these predictors.

Autonomous artificial intelligence versus teleophthalmology for diabetic retinopathy.

Purpose: To assess the role of artificial intelligence (AI) based automated software for detection of Diabetic Retinopathy (DR) compared with the evaluation of digital retinography by two double masked retina specialists. Methods: Two-hundred one patients (mean age 65 ± 13 years) with type 1 diabetes mellitus or type 2 diabetes mellitus were included. All patients were undergoing a retinography and spectral domain optical coherence tomography (SD-OCT, DRI 3D OCT-2000, Topcon) of the macula. The retinal photographs were graded using two validated AI DR screening software (Eye Art TM and IDx-DR) designed to identify more than mild DR. Results: Retinal images of 201 patients were graded. DR (more than mild DR) was detected by the ophthalmologists in 38 (18.9%) patients and by the AI-algorithms in 36 patients (with 30 eyes diagnosed by both algorithms). Ungradable patients by the AI software were 13 (6.5%) and 16 (8%) for the Eye Art and IDx-DR, respectively. Both AI software strategies showed a high sensitivity and specificity for detecting any more than mild DR without showing any statistically significant difference between them. Conclusions: The comparison between the diagnosis provided by artificial intelligence based automated software and the reference clinical diagnosis showed that they can work at a level of sensitivity that is similar to that achieved by experts.